BEAMing up for detection and quantification of rare sequence variants
Abstract
BEAMing allows the one-to-one conversion of a population of DNA fragments into a population of beads. We used rolling circle amplification to increase the number of copies bound to such beads by more than 100-fold. This allowed enumeration of mutant and wild-type sequences even when they were present at ratios less than 1:10,000 and was sensitive enough to directly quantify the error rate of DNA polymerases used for PCR.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The sensitivity of RAS mutation testing methods ranges from 10 to 25% for direct sequencing (least sensitive) to less than 1% for BEAMing (most sensitive), with other methods generally having sensitivities of 1-10%.
“The sensitivity of these methods ranged from 10 to 25% for direct sequencing (the least sensitive) to less than 1% for BEAMing (the most sensitive), with other methods generally having sensitivities of 1–10% [49,50]”
From The Role of KRAS Mutations in Colorectal Cancer: Biological Insights, Clinical Implications, and Future Therapeutic Perspectives (2025) · cites this paper as [49]
Cites
Genome sequencing in microfabricated high-density picolitre reactors
Margulies, M., Egholm, M., Altman, W. E., Attiya, S., Bader, J. S., Bemben, L. A., Berka, J., Braverman, M. S., Chen, Y.-J., Chen, Z., et al. (2005) · Nature · doi:10.1038/nature03959 · Cited by 7,693 · see citing works
Mutation detection and single-molecule counting using isothermal rolling-circle amplification
Lizardi, P. M., Huang, X. C., Zhu, Z., Bray‐Ward, P., Thomas, D. C., & Ward, D. C. (1998) · Nature Genetics · doi:10.1038/898 · Cited by 1,443 · see citing works
Accurate Multiplex Polony Sequencing of an Evolved Bacterial Genome
Shendure, J., Porreca, G. J., Reppas, N. B., Lin, X., McCutcheon, J. P., Rosenbaum, A. M., Wang, M. D., Zhang, K., Mitra, R. D., & Church, G. M. (2005) · Science · doi:10.1126/science.1117389 · Cited by 1,402 · see citing works
Detection and quantification of mutations in the plasma of patients with colorectal tumors
Diehl, F., Li, M., Dressman, D., He, Y., Shen, D., Szabo, S., Diaz, L. A., Goodman, S. N., David, K. A., Juhl, H., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507904102 · Cited by 1,188 · see citing works
Self-citationMan-made cell-like compartments for molecular evolution
Tawfik, D. S., & Griffiths, A. D. (1998) · Nature Biotechnology · doi:10.1038/nbt0798-652 · Cited by 960 · see citing works
Dressman, D. C., Yan, H., Traverso, G., Kinzler, K. W., & Vogelstein, B. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1133470100 · Cited by 845 · see citing works
Self-citationFidelity of DNA synthesis by the Thermus aquaticus DNA polymerase
Tindall, K. R., & Kunkel, T. A. (1988) · Biochemistry · doi:10.1021/bi00416a027 · Cited by 811 · see citing works
Larsson, C., Koch, J., Nygren, A. O. H., Janssen, G. M. C., Raap, A. K., Landegren, U. D., & Nilsson, M. F. (2004) · Nature Methods · doi:10.1038/nmeth723 · Cited by 332 · see citing works
LigAmp for sensitive detection of single-nucleotide differences
Shi, C., Eshleman, S. H., Jones, D. C., Fukushima, N., Li, H., Parker, A. R., Yeo, C. J., Hruban, R. H., Goggins, M., & Eshleman, J. R. (2004) · Nature Methods · doi:10.1038/nmeth713 · Cited by 127 · see citing works
Quantification of random genomic mutations
Bielas, J. H., & Loeb, L. A. (2005) · Nature Methods · doi:10.1038/nmeth751 · Cited by 99 · see citing works
A sensitive scanning technology for low frequency nuclear point mutations in human genomic DNA
Li‐Sucholeiki, X., & Thilly, W. G. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.9.e44 · Cited by 35 · see citing works
Liu, Q., & Sommer, S. S. (2004) · BioTechniques · doi:10.2144/04361dd03 · Cited by 31 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies
Bettegowda, C., Sausen, M., Leary, R. J., Kinde, I., Wang, Y., Agrawal, N., Bartlett, B. R., Wang, H., Luber, B., Alani, R. M., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007094 · Cited by 5,067 · see citing works
Self-citationHigh-throughput droplet digital PCR system for absolute quantitation of DNA copy number
Hindson, B. J., Ness, K. D., Masquelier, D. A., Belgrader, P., Heredia, N. J., Makarewicz, A. J., Bright, I. J., Lucero, M. Y., Hiddessen, A. L., Legler, T. C., et al. (2011) · Analytical Chemistry · doi:10.1021/ac202028g · Cited by 2,792 · see citing works
Liquid Biopsies: Genotyping Circulating Tumor DNA
Diaz, L. A., & Bardelli, A. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2012.45.2011 · Cited by 2,210 · see citing works
Huggett, J. F., Foy, C. A., Benes, V., Emslie, K., Garson, J. A., Haynes, R., Hellemans, J., Kubista, M., Mueller, R. D., Nolan, T., et al. (2013) · Clinical Chemistry · doi:10.1373/clinchem.2013.206375 · Cited by 859 · see citing works
Oxnard, G. R., Hu, Y., Mileham, K. F., Husain, H., Costa, D. B., Tracy, P., Feeney, N., Sholl, L. M., Dahlberg, S. E., Redig, A. J., et al. (2018) · JAMA Oncology · doi:10.1001/jamaoncol.2018.2969 · Cited by 686 · see citing works
Ice as a protocellular medium for RNA replication
Attwater, J., Wochner, A., Pinheiro, V. B., Coulson, A., & Holliger, P. (2010) · Nature Communications · doi:10.1038/ncomms1076 · Cited by 165 · see citing works
Takeda, M., Yoshida, S., Inoue, T., Sekido, Y., Hata, T., Hamabe, A., Ogino, T., Miyoshi, N., Uemura, M., Yamamoto, H., et al. (2025) · Cancers · doi:10.3390/cancers17030428 · Cited by 82 · see citing works
- Authors
- Li, M., Diehl, F., Dressman, D., Vogelstein, B., & Kinzler, K. W.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Vogelstein, Bert
- Kinzler, Kenneth W
- Venue
- Nature Methods
- Published
- 2006-01-23
- Volume
- 3
- Issue
- 2
- Pages
- 95-97
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- OpenAlex
- W1988290769
- Cited by
- 261
- References
- 12
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 4 · 2023: 9 · 2022: 11 · 2021: 12 · 2020: 14 · 2019: 23 · 2018: 23 · 2017: 18 · 2016: 24 · 2015: 8 · 2014: 15 · 2013: 9 · 2012: 11
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Methods (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Colorectal Cancer Alliance
- National Institutes of Health
- National Cancer Institute (CA 57345, CA43460, P50CA062924, CA 62924)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Molecular Biology Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- beaming, rare variant detection, rolling circle amplification, DNA sequencing
- MeSH terms
- DNA, DNA Mutational Analysis, DNA-Directed DNA Polymerase, Emulsions, Exons, Flow Cytometry, Fluorescent Dyes, Microscopy, Fluorescence, Microspheres, Mutation, Oils, Water, Reproducibility of Results, Polymerase Chain Reaction, Tumor Suppressor Protein p53, Nucleic Acid Amplification Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
